title: RanBPM interacts with TβRI, TRAF6 and curbs TGF induced nuclear accumulation of TβRI.
abstract: Transforming growth factor β (TGF-β), a cytokine, and its receptors play a vital role during normal embryogenesis, cell proliferation, differentiation, apoptosis and migration. Ran-binding protein in the microtubule-organizing center (RanBPM) serves as a scaffold protein that has been shown to interact with many other proteins, such as MET, Axl/Sky, TRAF6, IFNR, TrKA and TrkB in addition to p75NTR. In the current study, we have identified RanBPM as a novel binding partner of TβRI by yeast two-hybrid assay. The TβRI and RanBPM association was confirmed by co-immunoprecipitation and GST pull-down experiments. Additionally, expression of RanBPM abrogated the interaction between TβRI and TRAF6. Furthermore, RanBPM could depress TGF-β induced TRAF6 ubiquitination, subsequent NF-κB signaling pathway, and block TGF-β induced TβRI nuclear accumulation. Taken together, our results reveal that RanBPM may modulate TGF-β-mediated downstream signaling and biological functions.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
authors.forename: Junwen
authors.initials: J
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Ma
authors.forename: Shuo
authors.initials: S
authors.lastname: Tian
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Fan
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.forename: Qiaojiajie
authors.initials: Q
authors.lastname: Zhao
authors.forename: Kuan
authors.initials: K
authors.lastname: Tan
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Deng
authors.initials: D
authors.lastname: Chen
authors.forename: Bing-Ren
authors.initials: BR
authors.lastname: Huang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism*; D016384:Consensus Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9; D018125:Receptors, Transforming Growth Factor beta; D048029:TNF Receptor-Associated Factor 6; D016212:Transforming Growth Factor beta
keywords: Interaction; MAP; NF-κB; Ran-binding protein in the microtubule-organizing center; RanBPM; TACE; TAK1; TGF-β; TGF-β type I receptor; TGF-β type II receptor; TNF-alpha converting enzyme; TRAF6; TβRI; TβRII; Ubiquitination; mitogen-activated protein; nuclear factor KB; transforming growth factor (TGF)-activated kinase 1; transforming growth factor β; tumor necrosis factor (TNF)-receptor-associated factor 6